The goal of this project is to develop a micromachined, multielectrode microprobe capable of detecting multiple analytes, e.g., glutamate and dopamine, simultaneously in near real-time in the brains of live rodents. Glutamate and dopamine are neurotransmitters whose imbalance has been linked to neurological disorders such as Huntington's disease and Parkinson's disease. The envisioned microprobe would be a powerful new tool for the elucidation of the mechanisms behind such neurological disorders. This project is a collaborative effort among engineers and a neuroscientist that aims to design and fabricate the microprobes with an on- probe reference microelectrode as well as microelectrodes engineered for the selective electrochemical detection of both glutamate and dopamine simultaneously. The microprobe also will be characterized fully and tested both in vitro and in vivo. Over 100 devices will be constructed simultaneously on four-inch silicon wafers with two to five micron-sized electrodes per probe using micro-electro-mechanical-systems (MEMS) fabrication technologies. One or more microelectrode sites per probe will be chemically modified with permselective polymer films and immobilized glutamate oxidase for the electroenzymatic detection of glutamate. A novel technology to encapsulate glutamate oxidase in porous polymer nanoparticles will be used to improve enzyme stability and to enable its selective electrodeposition on microelectrodes. Dopamine will be detected at one or more microelectrode sites modified for the rapid, direct electrooxidation of this analyte. These microprobes will serve as a platform for the creation of additional multi-analyte sensing devices useful for measurements in vivo. PUBLIC HEALTH RELEVANCE: The goal of this project is to produce a microsensor that can be used by neuroscientists to measure changes in the levels of multiple chemical species simultaneously in the brains of laboratory rodents. This new tool will lead to the discovery of new fundamental knowledge on important neurological disorders including Parkinson's disease.